Lizong Dai

Gold@Polymer Nanostructures with Tunable Permeability Shells for Selective Catalysis

National Natural Science Foundation of China [50873082, 50903067]; Scientific and Technical Project of Fujian Province of China [2009J1009, 2010H6021]

Orthogonally Functionalized Nanoscale Micelles for Active Targeted Codelivery of Methotrexate and Mitomycin C with Synergistic Anticancer Effect

The design of nanoscale drug delivery systems for the targeted codelivery of multiple therapeutic drugs still remains a formidable challenge (ACS Nano, 2013, 7, 9558-9570; ACS Nano, 2013, 7, 9518-9525). In this article, both mitomycin C (MMC) and methotrexate (MTX) loaded DSPE-PEG micelles (MTX-M-MMC) were prepared by self-assembly using the dialysis technique, in which MMC-soybean phosphatidylcholine complex (drug-phospholipid complex) was encapsulated within MTX-functionalized DSPE-PEG micelles. MTX-M-MMC could coordinate an early phase active targeting effect with a late-phase synergistic anticancer effect and enable a multiple-responsive controlled release of both drugs (MMC was released in a pH-dependent pattern, while MTX was released in a protease-dependent pattern). Furthermore, MTX-M-MMC could codeliver both drugs to significantly enhance the cellular uptake, intracellular delivery, cytotoxicity, and apoptosis in vitro and improve the tumor accumulation and penetration and anticancer effect in vivo compared with either both free drugs treatment or individual free drug treatment. To our knowledge, this work provided the first example of the systemically administrated, orthogonally functionalized, and self-assisted nanoscale micelles for targeted combination cancer chemotherapy. The highly convergent therapeutic strategy opened the door to more simplified, efficient, and flexible nanoscale drug delivery systems.

Study on the binding of chloroamphenicol with bovine serum albumin by fluorescence and UV-vis spectroscopy

The binding of chloroamphenicol (CPC) to bovine serum albumin (BSA) at 296 K, 303 K, and 310 K by fluorescence and UV-visible absorption spectroscopy were investigated under imitated physiological conditions. The experimental results showed that the fluorescence quenching mechanism between CPC and BSA was combined quenching (dynamic and static quenching) procedure at low CPC concentration, or a dynamic quenching procedure at high concentrations. The binding constants, binding sites and the corresponding thermodynamic parameters of the interaction system were calculated. According to Förster non-radiation energy transfer theory, the binding distance between CPC and BSA was calculated to be 3.02 nm. Both synchronous fluorescence and FT-IR spectra confirmed the interaction, and indicated the conformational changes of BSA. The effects of some common metal ions Ca(2+), Ni(2+), Mg(2+), Fe(2+), and Cu(2+) on the binding constant between CPC and BSA were examined. Furthermore, we investigated the possible sub-domains on BSA that bind CPC by displacement experiments.

Self-Assembled Nanoparticles Based on Amphiphilic Anticancer Drug–Phospholipid Complex for Targeted Drug Delivery and Intracellular Dual-Controlled Release

Integrating advantages of mitomycin C (MMC)-phospholipid complex for increased drug encapsulation efficiency and reduced premature drug release, DSPE-PEG-folate (DSPE-PEG-FA) for specific tumor targeting, we reported a simple one-pot self-assembly route to prepare the MMC-phospholipid complex-loaded DSPE-PEG-based nanoparticles (MP-PEG-FA NPs). Both confocal imaging and flow cytometry demonstrated that MMC was distributed into nuclei after cellular uptake and intracellular drug delivery. More importantly, the systemically administered MP-PEG-FA NPs led to increased blood persistence and enhanced tumor accumulation in HeLa tumor-bearing nude mice. This study introduces a simple and effective strategy to design the anticancer drug-phospholipid complex-based targeted drug delivery system for sustained/controlled drug release.

A Simple Dual-pH Responsive Prodrug-Based Polymeric Micelles for Drug Delivery

To precisely deliver drug molecules at a targeted site and in a controllable manner, there has been great interest in designing a synergistical drug delivery system that can achieve both surface charge-conversion and controlled release of a drug in response to different stimuli. Here we outline a simple method to construct an intelligent drug carrier, which can respond to two different pH values, therefore achieving charge conversion and chemical-bond-cleavage-induced drug release in a stepwise fashion. This drug carrier comes from the self-assembly of a block copolymer-DOX conjugate synthesized through a Schiff base reaction between poly(2-(diisopropylamino)ethyl methacrylate-b-poly(4-formylphenyl methacrylate-co-polyethylene glycol monomethyl ether methacrylate) (PDPA-b-P(FPMA-co-OEGMA)) and DOX. The surface charge of the BCP-DOX micelles reversed from negative to positive when encountering a weakly acidic environment due to the protonation of PDPA segments. In vitro cellular uptake measurement shows that the cellular uptake and internalization of the BCP-DOX micelles can be significantly enhanced at pH ∼ 6.5. Moreover, this drug carrier exhibits a pH-dependent drug release owing to the cleavage of the imine bond at pH < 5.5. With this dual-pH responsive feature, these micelles may have the ability to precisely deliver DOX to the cancer cells.

Modification of epoxy resin through the self-assembly of a surfactant-like multi-element flame retardant

In order to develop a multi-element, synergistic, flame-retardant system, the combination of DOPO, POM and POSS was achieved using the classical Kabachnik–Fields reaction. The as-designed POSS-bisDOPO was characterized by FT-IR, 1H NMR, 13C NMR, 31P NMR, 2D NMR, and MS. POSS-bisDOPO was introduced into epoxy resins to obtain flame-retardant materials. The LOI value can reach 34.5% when the content of POSS-bisDOPO is 20 wt%. The TGA results showed that the char yield was significantly improved in cured POSS-bisDOPO/EP. The ATR-FTIR results, optical images and SEM analyses indicated that the residual char had a compact and coherent appearance in the inner layer, while the outer structure was intumescent and multi-porous. Therefore, by isolating heat and oxygen more efficiently, the char played an important role in improving the thermal stability and flame retardancy of cured POSS-bisDOPO/EP. The three-point bending test results showed that the mechanical strength of POSS-bisDOPO/EP was higher than those of pure EP and POSS–NH2/EP due to the outstanding reinforcement effect of the unique nanostructure of POSS-bisDOPO assembled in the EP matrix. These data indicated that POSS-bisDOPO not only obviously enhances the flame retardancy, but also improves the mechanical properties of epoxy resins.

CuO based inorganic-organic hybrid nanowires: a new type of highly sensitive humidity sensor

The organic surfactant template method has been widely used for the preparation of CuO nanorods, nanotubes and nanowires. However, the surfactants in this system have no effect on the properties of the final products because they are flushed away. In this work, we used this method to synthesize a novel type of inorganic-organic hybrid nanowire via the hybridization between CuO and amphiphilic oligomer octadecyl, polyethylene glycol di-butenetrioate (O-B-EG-B). Here O-B-EG-B, as a structure director, was not flushed away but remained in the prepared hybrid nanowires because it was bound around CuO or entrapped in interior CuO. The hybrid nanowires showed CuO cores and P(O-B-EG-B) shells when the concentration of O-B-EG-B was 0.4 mg ml(-1), but exhibited P(O-B-EG-B) cores and CuO shells when the concentration of O-B-EG-B was 4.0 mg ml(-1). We found that the hybrid nanowires with P(O-B-EG-B) cores and CuO shells could sense a slight change in the relative humidity (RH) and respond by rapidly changing their conductivity. The resistance changed by about two orders of magnitude within the humidity range from 5% to 83.8%. Moreover, a humidity sensor based on this type of nanowire not only showed long-term stability but also exhibited excellent reversibility to moisture changes in air.

Novel methotrexate prodrug-targeted drug delivery system based on PEG–lipid–PLA hybrid nanoparticles for enhanced anticancer efficacy and reduced toxicity of mitomycin C

In the present study we have investigated novel MTX prodrug-targeted and MMC-loaded PLA-lipid-PEG hybrid NPs. These employ a double emulsion solvent evaporation method for the introduction of an anticancer drugs moiety of the MMC-soybean phosphatidylcholine complex or DSPE-PEG-MTX, in which the MTX prodrug can be exploited as a targeting ligand. The prepared drug delivery systems present a spherical shape, a small particle size (219.6 ± 2.1 nm) with narrow particle size distribution, high MMC encapsulation efficiency (90.5 ± 3.0%) and a sustained and pH-controlled MMC release. The advantage of the new drug delivery systems is that the two-anticancer drug moiety can coordinate the early-phase targeting effect with the later-phase anticancer effect. In vivo pharmacokinetics, following intravenous administration of the drug delivery systems, indicates a prolonged systemic circulation time of MMC. More importantly, the drug delivery systems exhibited a significant accumulation of MMC in the nuclei as the site of MMC action, which was indicative of the enhancement of anticancer activity. Such a design of drug delivery systems may open up a new horizon for targeted delivery and sustained and controlled release of MMC.

Composite supramolecular nanoassemblies with independent stimulus sensitivities

Nanoscale assemblies with stimuli-sensitive features have attracted significant attention due to implications in a variety of areas ranging from materials to biology. Recently, there have been excellent developments in obtaining nanoscale structures that are concurrently sensitive to multiple stimuli. Such nanostructures are primarily focused on a single nanostructure containing an appropriate combination of functional groups within the nanostructure. In this work, we outline a simple approach to bring together two disparate supramolecular assemblies that exhibit very different stimuli-sensitive characteristics. These composite nanostructures comprise a block copolymer micelle core and nanogel shell, both of which can preserve their respective morphology and stimulus sensitivities. The block copolymer is based on poly(2-(diisopropylamino)ethylmethacrylate-b-2-aminoethylmethacrylate hydrochloride), which contains a pH-sensitive hydrophobic block. Similarly, the redox-sensitive nanogel is derived from a poly(oligoethyleneglycolmonomethylethermethacrylate-co-glycidylmethacrylate-co-pyridyldisulfide ethylmethacrylate) based random copolymer. In addition to the independent pH-response of the micellar core and redox-sensitivity of the nanogel shell in the composite nanostructures, the synergy between the micelles and the nanogels have been demonstrated through a robust charge generation in the nanogels during the disassembly of the micelles. The supramolecular assembly and disassembly have been characterized using transmission electron microscopy, dynamic light scattering, zeta potential measurements, fluorescence spectroscopy and cellular uptake.

Responsive single-chain polymer nanoparticles with host–guest features

We report a facile approach to form ultra-fine single-chain polymer nanoparticles (SCPNs) via disulfide-based intrachain crosslinking of single polymer chains of a random copolymer poly(HEMA-co-PDSEMA). The SCPNs, which were prepared under mild reaction conditions and at normal reaction concentrations (up to 10 mg mL−1), have been characterized by 1H nuclear magnetic resonance (1H NMR) spectroscopy, atomic force microscopy (AFM), differential scanning calorimetry (DSC), gel permeation chromatography (GPC), and dynamic light scattering (DLS). The influences of the crosslinking density, the molecular weight and the initial concentration of the polymer upon the formation of SCPNs are also reported. In order to investigate the hydrophobic interior of SCPNs, we trace the emission spectrum of a pyrene probe. We highlight that these SCPNs exhibit host–guest properties to stably encapsulate hydrophobic guest molecules and release them in response to a redox stimulus.